Is PRMT6 p.Val54Phe (c.160G>T) pathogenic?

PRMT6 p.Val54Phe (c.160G>T) is classified Uncertain significance in PRMT6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: ambiguous (0.5); Very rare (popmax 0.00703%, nfe).

How common is PRMT6 p.Val54Phe (c.160G>T) in the general population?

PRMT6 p.Val54Phe (c.160G>T) is very rare (popmax 0.00703%, nfe) (gnomAD).

What do computational predictors say about PRMT6 p.Val54Phe (c.160G>T)?

AlphaMissense predicts ambiguous (score 0.5) — an in-silico prediction, not a clinical call.

PRMT6 p.Val54Phe

c.160G>T · rs755978736 · VCV3218936

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00703%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5	ambiguous
REVEL	0.286	benign-leaning
SaProt	LLR -2.67	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.93, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 1,124 bp · p 0.55 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00703% European (non-Finnish) · 83/1,179,834 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00533%

Overall 0.00539% 87/1,613,612 alleles · very rare exomes 82/1,461,354 · genomes 5/152,258 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00703%	14,215
Remaining individualsnot grpmax-eligible	0.0048%	20,821
African / African-American	0.00133%	74,950

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PRMT6
Protein: p.Val54Phe
Coding: c.160G>T
MANE Select: NM_018137
dbSNP: rs755978736
Type: single nucleotide variant
Location: chr1:107056875 (GRCh38)
Gene constraint: LOEUF 1.052 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.80 · 13 PDB
Residue 54: the sam-dependent mtase prmt-type domain; an α-helix

Full PRMT6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRMT6 p.Ala254Gly Uncertain significance ★ ⚠ same type
PRMT6 p.Ala261Pro Uncertain significance ★ ⚠ same type
PRMT6 p.Ala261Thr Uncertain significance ★ ⚠ same type
PRMT6 p.Ala315Ser Uncertain significance ★ ⚠ same type
PRMT6 p.Ala321Gly Uncertain significance ★ ⚠ same type
PRMT6 p.Arg347Gly Uncertain significance ★ ⚠ same type
PRMT6 p.Arg347Trp Uncertain significance ★ ⚠ same type
PRMT6 p.Arg351His Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/prmt6-p-val54phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown